Background
Randomized phase III AEGEAN trial, N=802, in resectable stage II–IIIB (N2) NSCLC, excluding EGFR/ALK alterations from the efficacy analysis. Patients were treatment-naive.
Interventions and follow up
Arm A: Durvalumab 1500 mg IV Q3W + platinum-based chemotherapy for 4 cycles (neoadjuvant) → surgery → durvalumab IV Q4W for 12 cycles (adjuvant)
Arm B: Placebo IV Q3W + platinum-based chemotherapy for 4 cycles (neoadjuvant) → surgery → placebo Q4W for 12 cycles (adjuvant)
Primary endpoint: EFS, pCR
mFollow up: 11.7 mo
Arm B: Placebo IV Q3W + platinum-based chemotherapy for 4 cycles (neoadjuvant) → surgery → placebo Q4W for 12 cycles (adjuvant)
Primary endpoint: EFS, pCR
mFollow up: 11.7 mo
Results
Definitive surgery: ~77% each group
R0 resection: 94.7% vs 91.3%
Completed 12 cycles adjuvant: 24.0% (durvalumab) vs 21.1% (placebo)
EFS: not reached vs not reached; 12-mo EFS 73.4% vs 64.5%, HR 0.68, 95% CI 0.53–0.88, P=.004
OS: not reported at interim analysis
ORR: 56.3% vs 38.0%
pCR: 17.2% vs 4.3%
R0 resection: 94.7% vs 91.3%
Completed 12 cycles adjuvant: 24.0% (durvalumab) vs 21.1% (placebo)
EFS: not reached vs not reached; 12-mo EFS 73.4% vs 64.5%, HR 0.68, 95% CI 0.53–0.88, P=.004
OS: not reported at interim analysis
ORR: 56.3% vs 38.0%
pCR: 17.2% vs 4.3%
Adverse events
Overall: Grade 3–4 adverse events 42.4% vs 43.2%
Immune-mediated: 23.7% vs 9.3%
Immune-mediated: 23.7% vs 9.3%
Conclusions
Perioperative durvalumab with neoadjuvant chemotherapy significantly improved EFS and pCR in resectable NSCLC, with a safety profile consistent with the known effects of the individual agents.
Key Limitations
Short follow-up (11.7 mo) with immature OS; EGFR/ALK excluded from efficacy; relative contribution of neoadjuvant vs adjuvant durvalumab not isolated.
Clinical Context
Perioperative durvalumab + chemotherapy is FDA/EMA approved for resectable NSCLC, an established perioperative chemoimmunotherapy option per ASCO/ESMO.